CMV is a major cause of inflammatory organ disease in immunosuppressed patients. To elucidate the mechanisms of CMV-induced inflammation, tumor necrosis factor (TNF-alpha) was studied in AIDS patients with CMV colitis. In situ hybridization techniques were used on colonic mucosa from AIDS patients and normal controls. Positive hybridization of TNF- alpha probe to mRNA was obtained with colonic mucosa from patients, and was associated with CMV, but not HIV-1 infected cells. Also, a patient derived isolate of CMV induced primary human blood monocytes to express TNF-alpha mRNA and increased the levels of secreted TNF-alpha. Thus, CMV induction of TNF-alpha may play a central role in CMV-induced inflammation. Furthermore, because of the known effects of TNF-alpha on the expression of HIV-1 provirus, CMV may be a co-factor in activation of latent HIV-1, without the requirement for co-infection of cells by the two viruses.